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Indian Pediatr 2009;46: 19-21 |
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Performance Evaluation for Neonatal
Phototherapy |
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Vinod K Bhutani
Professor, Department of Pediatrics, Division of Neonatal
and Developmental Medicine,
Stanford University School of Medicine and Lucile Packard Children’s
Hospital, 750 Welch Ave #315;
Stanford, CA 94304, USA.
E-mail: [email protected]
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P hototherapy is
the current "drug" of choice to reduce the severity of neonatal
unconjugated hyperbilirubinemia regardless of its etiology and its
implementation requires a technical framework that conforms to existing
guidelines that promote its safer and effective use(1). Optimal use of
phototherapy has been defined by specific ranges of total serum bilirubin
thresholds configured to an infant’s postnatal age (in hours) and
potential risk for bilirubin neurotoxicity(1). Effective phototherapy
implies its use as a "drug" at specific blue light wavelengths (peak, 460
to 500 nm) and emission spectrum (range, 400 to 520 nm), preferably in a
precise (narrow) bandwidth, that is delivered at an irradiance (dose) of
³30-35
µW/cm2/nm to upto 80% of an infant’s body surface area (BSA). Radiation
with visible light above about 500 nm is considered useless.
Clinical response to a specific phototherapy modality
is dependent on a number of confounding factors that include ongoing rate
of bilirubin production and maturation of enterohepatic elimination
processes. As described by Maisels and McDonagh(2), the absorption of
light by the normal form of bilirubin (4Z,15Z-bilirubin)
generates transient excited-state bilirubin molecules. These fleeting
intermediates can react with oxygen to produce colorless products of lower
molecular weight, or they can undergo rearrangement to become structural
isomers (lumirubins) or isomers in which the configuration of at least one
of the two Z-configuration double bonds has changed to an E
configuration. (Z and E, from the German zusammen
(together) and entgegen (opposite), respectively, are prefixes used
for designating the stereochemistry around a double bond. The prefixes 4
and 15 designate double-bond positions. Only the two principal
photoisomers formed in humans are well described(3). Configurational
isomerization is reversible and much faster than structural isomerization,
which is irreversible. Both occur much more quickly than photo-oxidation.
The photoisomers are less lipophilic than the 4Z,15Z form of
bilirubin and can be excreted unchanged in bile without undergoing
glucuronidation. Lumirubin isomers can also be excreted in urine. On the
other hand, photo-oxidation products are excreted mainly in urine. Once in
bile, configurational isomers revert spontaneously to the natural 4Z,15Z
form of bilirubin. Overall, photoisomerization rather than
photodegradation appears to play a more significant role in bilirubin
elimination. Photoisomers products form more rapidly on exposure to
phototherapy and appear in blood long before the plasma bilirubin begins
to decline. The rate of bilirubin elimination depends on the rates of
formation as well as the rates of clearance of these photoproducts.
Over the past 4 decades, a variety of novel strategies
have been proposed to enhance the effectiveness of phototherapy(4).
Currently, there are limited standardized processes to assess performance
of devices or delivery methods for phototherapy. Assessment for efficacy
of phototherapy is influenced by: (a) optimization of light
administration to achieve a minimum distance between the device and the
patient such that the foot print of light covers maximum BSA with minimal
physical barriers; (b) infant characteristics such as the severity
of jaundice, body surface proportions, tissue dermal thickness,
pigmentation, and perfusion; and (c) the duration of treatment to a
specific bilirubin threshold. To better investigate the operation of
phototherapy devices in clinical practice, the following technical factors
need to be considered.
1. Use of potent light source, as defined by its
bandwidth and peak emission and its ability to penetrate deeper tissues,
is addressed by: (a) use blue lights (at a narrow spectrum with a
specific peak wavelength (460 to 500 nm) and a range of emission spectrum
(400 to 520 nm) directed at the infant skin; (b) avoidance of
concurrent overheating of the infant; (c) minimizing the
confounding effect on other biological pigments; (d) diminishing
contamination with ultraviolet (UV) lights; and (e) assessing the
formation of bilirubin photoisomer by-products that confound total serum
bilirubin measurements and may impact bilirubin binding ability to
albumin.
2. The light dose, as determined by its irradiance
or intensity, at which photons are delivered to the body surface per cm 2
of the exposed skin. The quantitative measure is µW/cm2/nm. To compare
spectral irradiance measurements adjusted to specific light
wavelength, Vreman, et al.(5) recommend that a calibrated
BiliBlanket Meters I and II (Ohmeda, GE Healthcare) yield identical
results with stable output of phototherapy light sources. This type of
meter was selected from the several devices with different photonic
characteristics that are commercially available, because it has a wide
sensitivity range (400–520nm with peak sensitivity at 450nm), which
overlaps the unconjugated bilirubin absorption spectrum and which renders
it suitable for the evaluation of narrow and broad wavelength band light
sources. These two devices were found to be exceptionally stable during
several years of use, and agreed closely after each annual calibration.
Though the device is capable of measuring irradiance with a sensitivity of
0.1 µW/cm2/nm, this level of sensitivity is clinically unnecessary.
Increasing the footprint of the light (by increasing the distance) from a
single light source can lead to reduced irradiance. Vreman, et al.(5)
have also described a unique and optimal technique to assess uniformity of
irradiance distribution in the footprint of the light.
3. Extent of total light exposure, described as
treatable BSA that can be exposed to the device. This may be achieved with
the use special blue tubes (BB), by bringing the light source as close to
baby as possible. A "spot" halide lamp cannot be used in this manner
because of danger due to heat and possible burn. Placing the baby in a
bassinet rather than in an incubator provides for an unimpeded exposure to
a light source. Alternatively, the light source could be placed within the
incubator to avoid exposure through the incubator wall. Performance and
integrity of the light sources should be checked for dosage with a
equipment-specific radiometer with a recognition that irradiance
will vary widely depending on where the measurement is taken. The
International Electrotechnical Commission defines the treatment as
"effective surface area" of 60×30cm to assess phototherapy devices.
However, clinical use and comparison would require an adjustment to a
3-dimensional surface area as well account for infants of varying BSA
proportions. Planar (anterior or, posterior) exposure accounts for about
35% of the BSA. In preterms, the head is disproportionately larger and the
patched area can be more extensive. Thus, while ensuring protection for
the retina and male gonads and diaper protection for hygiene, a maximal
area that could receive consistent irradiance is about 80% of the total
BSA (circumferential phototherapy).
An insight to the clinical goal, reduction in duration
of phototherapy (in hours), is characterized by an evident reversal in
rate of rise in total serum (a reduction of >2 mg/dL within 4 to 6 hours
of its initiation, about 0.5mg/dL/hr). Response depends on the rate of
bilirubin production as well as the effective dosage of light source. In a
study reported in this issue of Indian Pediatrics, Sivanandan,
et al. (6) investigate the previously reported claims of slings made
of white reflective material in increasing efficacy of a single-surface
compact fluorescent light phototherapy. Through a systematic clinical
study design, they were unable to verify a reduction in the duration of
phototherapy on addition of slings to phototherapy units. The marginally
higher measured irradiance of phototherapy with use of sling was not
clinically relevant. Absence of a remarkable therapeutic advantage
concurrent with potential risks of shielding the infant from direct visual
observation as well as the hygienic impediments of the shields precludes
the use of opaque reflective materials. Although apparently safe for the
term infant and larger preterm infants, the application of higher
irradiance to the much smaller, more translucent, and less mature preterm
infant, who generally is subjected to longer periods of phototherapy, has
never been studied systematically. The risks of phototherapy when applied
to thin, translucent, antioxidant-insufficient infants have yet to be
delineated for a prudent duration of exposure.
In the meantime, our search for evidence-based low cost
strategies for safe and effective phototherapy and enhanced "drug
delivery" system continues.
Funding: None.
Competing interests: None stated.
References
1. American Academy of Pediatrics. Management of
hyperbilirubinemia in the newborn infant 35 or more weeks of gestation.
Pediatrics 2004; 114: 297-316.
2. Maisels MJ, McDonagh AF. Phototherapy for neonatal
jaundice. N Engl J Med 2008; 358: 920-928.
3. McDonagh AF, Lightner DA. Phototherapy and the
photobiology of bilirubin. Semin Liver Dis 1988; 8: 272-283.
4. McDonagh AF. Phototherapy: from ancient Egypt to the
new millennium. J Perinatol 2001; 21 Suppl 1: S7-S12.
5. Vreman HJ, Wong RJ, Murdock JR, Stevenson DK.
Standardized bench method for evaluating the efficacy of phototherapy
devices. Acta Paediatr 2008; 97: 308-316.
6. Sivanandan S, Chawla D, Misra, S, Agarwal R, Deorari
AK. Effect of sling application on efficacy of phototherapy in healthy
term neonates with non-hemolytic jaundice: a randomized study. Indian
Pediatr 2009; 46: 23-28. |
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